Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway

•Butyrate levels exhibited a decreasing trend with the progression of CKD.•Butyrate alleviated renal fibrosis in CKD mice.•Butyrate suppressed NLRP3-mediated pyroptosis.•Butyrate inhibited NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway. Chronic kidney disease (CKD) is a serious and irreve...

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Veröffentlicht in:International immunopharmacology 2023-11, Vol.124, p.111010-111010, Article 111010
Hauptverfasser: Tian, Xiaofang, Zeng, Yizhou, Tu, Qingxian, Jiao, Yang, Yao, Song, Chen, Ying, Sun, Li, Xia, Qianhang, Luo, Yadan, Yuan, Liying, Jiang, Qianfeng
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container_title International immunopharmacology
container_volume 124
creator Tian, Xiaofang
Zeng, Yizhou
Tu, Qingxian
Jiao, Yang
Yao, Song
Chen, Ying
Sun, Li
Xia, Qianhang
Luo, Yadan
Yuan, Liying
Jiang, Qianfeng
description •Butyrate levels exhibited a decreasing trend with the progression of CKD.•Butyrate alleviated renal fibrosis in CKD mice.•Butyrate suppressed NLRP3-mediated pyroptosis.•Butyrate inhibited NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway. Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. Hence, we suggest that butyrate may have a renoprotective role in CKD, alleviating renal fibrosis possibly by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway.
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Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. 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Chronic kidney disease (CKD) is a serious and irreversible disease primarily characterized by chronic inflammation and renal fibrosis. Recent studies have suggested that gut microbiota-related metabolites, particularly short-chain fatty acids (SCFAs) are significantly associated with kidney diseases. Notably, butyrate, a type of SCFAs, plays a crucial role in this correlation. However, the effect of butyrate on renal fibrosis in patients with CKD and its potential mechanisms remain unclear. In this study, we demonstrated that butyrate levels are reduced as CKD progresses using a CKD C57BL/6 mouse model established by a 0.2% adenine diet. Exogenous supplementation of butyrate effectively alleviated renal fibrosis and repressed the levels of proteins associated with NLRP3-mediated pyroptosis (NLRP3, IL-1β, caspase-1, and GSDMD). Additionally, we conducted an in vitro experiment using HK-2 cells, which also confirmed that the elevated levels of NLRP3-mediated pyroptosis proteins in TGF-β1-stimulated HK-2 cells are reversed by butyrate intervention. Further, butyrate mitigated the activity of the STING/NF-κB/p65 pathway, and STING overexpression impaired the protective function of butyrate in CKD. 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subjects NF-κB/p65
NLRP3 inflammasome
Pyroptosis
Renal fibrosis
Short-chain fatty acids
title Butyrate alleviates renal fibrosis in CKD by regulating NLRP3-mediated pyroptosis via the STING/NF-κB/p65 pathway
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